The present invention is directed to pharmaceutical compounds and compositions which are able to therapeutically modulate lipid and/or carbohydrate metabolism for the treatment of metabolic disorders and the diseases as well as de-myelinating and other neurodegenerative disorders of the central and peripheral nervous system. The inventive compounds of the present invention are comprised of phenyl and pyridinyl-1, 2,4-oxadiazolone derivatives and their physiologically acceptable salts and functional derivatives that are shown to provide peroxisome proliferator activator PPARdelta agonists have been described in the prior art. (e.g. WO 01/00603 and WO 02/092590 to Keil et. al., WO2003/074495, WO2004/093879, WO2004/080943, WO2005/054213 and WO2005/097786). Compounds comprising an oxadiazolone component have been disclosed as inhibitors of factor Xa and described in DE 101 12 768 A1 and also as orally administrable hypoglycemic agents in WO 96/13264. WO 97/40017 teaches oxadiazolone compounds having a phenyl group linked to Heterocyclic rings and these are disclosed as modulators of those molecules that comprise phosphotyrosine recognition units. Benzene derivatives of oxadiazolone compounds are known to be useful as inhibitors of squalene synthase and protein farnesyltransferase and these are described in WO96/34851. The present invention however, is directed to pharmaceutical compounds and compositions comprised of phenyl and pyridinyl-1,2,4-oxadiazolone derivatives and their physiologically acceptable salts and functional derivatives showing that exhibit peroxisome proliferator activator receptor (PPAR) delta agonist activity. PPARdelta agonists have are well in the biochemical and pharmaceutical arts. Phenyl derivatives of oxadiazalones are described as agents for the therapeutic treatment of thrombobolic disorders as described in WO 02/057236. Benzene derivatives of oxadiazalone have also been shown to inhibitor squalene synthase and protein farnesyltransferase as described in WO96/34851. See also U.S. Pat. No. 6,200,995 to De La Brouse-Elwood et. al. as well as WO 03/043997 and WO 02/092590 to Johnston et. al.
The peroxisome proliferator-activated receptors (PPAR) are transducer proteins belonging to the steroid/thyroid/retinoid receptor superfamily. The PPAR receptors were originally identified as orphan receptors without known ligands, but were known for their ability to mediate the pleiotropic effects of fatty acid peroxisome proliferators. These receptors function as ligand-regulated transcription factors that control the expression of target genes by binding to their responsive DNA sequences as heterodimers with RXR. The target genes encode enzymes involved in a number of metabolic and cell growth/cell proliferation/cell differentiation inductions. These then act as targets for the development of therapeutic agents for the treatment of metabolic and central nervous system disorders, among others.